USMLE® Step 1 style questions USMLE
A 9-year-old boy is brought to the emergency department by his parents due to prolonged bleeding following a tooth extraction earlier in the day. Past medical history is noncontributory. Temperature is 37.5°C (99.5°F), pulse is 88/min, respirations are 14/min, and blood pressure is 112/62 mmHg. Physical exam shows gingival bleeding and petechiae. Laboratory testing is obtained, and the results are shown below.
|Prothrombin time (PT)||12 seconds|
|Activated partial thromboplastin time (aPTT)||29 seconds|
|Bleeding time*||15 minutes|
Which of the following conditions is the patient at greatest risk of developing?
Content Reviewers:Rishi Desai, MD, MPH
‘Hemo’ refers to the blood, ‘lytic’ refers to breaking down, and ‘uremic’ refers to increased urea levels in the blood.
And this helps explain hemolytic uremic syndrome because the two main effects are destruction of red blood cells and the declining function of the kidney causing uremia - both of which result from tiny blood clots that form in tiny blood vessels - predominantly in the kidneys.
Classically, especially in children, hemolytic uremic syndrome is triggered by a bout of bloody diarrhea.
When that happens, it’s called diarrhea-positive or D positive hemolytic syndrome, sometimes shortened to HUS or simply typical HUS.
These numbers and letters refer to the specific antigens on the surface of the bacteria.
‘157’ refers to the O-antigen present in the lipopolysaccharide cell wall and ‘7’ refers to the H-antigen located on the flagella of the bacteria.
The toxin gets its name due to its structural similarity with shiga toxin produced by Shigella dysenteriae, another bacteria that causes bloody diarrhea and subsequent hemolytic uremic syndrome.
From there, the toxin is carried on the surface of these cells to the site of blood filtration - which is the glomerular capillaries of the kidney.
Endothelial cells lining these glomerular capillaries express a glycolipid receptor called globotriaosylceramide or Gb3-receptor that has an incredibly strong affinity for the shiga-like toxin - the receptor is like a little magnet that can simply snatch the toxin away from a white blood cell as it drifts by.
Once the toxin binds to the Gb3-receptor, it gets engulfed by the endothelial cell and once inside, it wreaks havoc on the cell.
The toxin prevents aminoacyl-tRNA, which is the little molecule that carries the amino acids to make proteins, from binding to the ribosome.
This stops all protein synthesis in the cell.
In addition to this it also leads to fragmentation of the DNA that activates apoptotic or cell-suicide pathways which causes the endothelial cell to die.
So when large numbers of kidney endothelial cells start undergoing apoptosis, lots of tiny blood clots start to form in the kidneys.
Another way that clots form is through a condition called thrombotic thrombocytopenic purpura or TTP.
In TTP, clots start to form inappropriately, and the underlying reason has to do with a molecule called von Willebrand factor or vWF - named for a Finnish doctor named Erik von Willebrand.
You can think of vWF as a very tiny piece of sticky tape that multiple platelets bind to and form a clot.
Under normal conditions, once time has passed and the clot has served its role, the von Willebrand factor protein gets chopped into small pieces by an enzyme that floats around in the blood called ADAMTS13.
In thrombotic thrombocytopenic purpura, the ADAMTS13 enzyme is not as active, which means that there is excess von Willebrand factor floating around in the blood, and that von Willebrand factor starts binding to platelets and forming clots willy-nilly throughout the body including the kidneys.
This inappropriate formation of clots also means that there are fewer platelets available when clots are actually needed.
Hemolytic-uremic syndrome (HUS) is a serious condition that's characterized by microangiopathic hemolytic anemia, thrombocytopenia, and renal failure. It is usually caused by E. coli O157:H7 infection and presents with fever, jaundice, stomach cramps, vomiting, and diarrhea. A person with HUS may also have a rash, red or purple dots on the skin, and tiredness.
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